Microfluidic devices developed in the early 1990s were fabricated from hard materials, such as silicon and glass, using photolithography and etching techniques. See Ouellette, J., The Industrial Physicist 2003, Aug./Sep., 14-17; Scherer, A., et al., Science 2000, 290, 1536-1539. Photolithography and etching techniques, however, are costly and labor intensive, require clean-room conditions, and pose several disadvantages from a materials standpoint. For these reasons, soft materials have emerged as alternative materials for microfluidic device fabrication. The use of soft materials has made possible the manufacture and actuation of devices containing valves, pumps, and mixers. See, e.g., Ouellette, J., The Industrial Physicist 2003, Aug./Sep., 14-17; Scherer, A., et al., Science 2000, 290, 1536-1539; Unger, M. A., et al., Science 2000, 288, 113-116; McDonald, J. C., et al., Acc. Chem. Res. 2002, 35, 491-499; and Thorsen, T., et al., Science 2002, 298, 580-584. For example, one such microfluidic device allows for control over flow direction without the use of mechanical valves. See Zhao, B., et al., Science 2001, 291, 1023-1026.
The increasing complexity of microfluidic devices has created a demand to use such devices in a rapidly growing number of applications. To this end, the use of soft materials has allowed microfluidics to develop into a useful technology that has found application in genome mapping, rapid separations, sensors, nanoscale reactions, ink-jet printing, drug delivery, Lab-on-a-Chip, in vitro diagnostics, injection nozzles, biological studies, and drug screening. See, e.g., Ouellette, J., The Industrial Physicist 2003, Aug./Sep., 14-17; Scherer, A., et al., Science 2000, 290, 1536-1539; Unger, M. A., et al., Science 2000, 288, 113-116; McDonald, J. C., et al., Acc. Chem. Res. 2002, 35, 491-499; Thorsen, T., et al., Science 2002, 298, 580-584; and Liu, J., et al., Anal. Chem. 2003, 75, 4718-4723.
Poly(dimethylsiloxane) (PDMS) is the soft material of choice for many microfluidic device applications. See Scherer, A., et al., Science 2000, 290, 1536-1539; Unger, M. A., et al., Science 2000, 288, 113-116; McDonald, J. C., et al., Acc. Chem. Res. 2002, 35, 491-499; Thorsen, T., et al., Science 2002, 298, 580-584; and Liu, J., et al., Anal. Chem. 2003, 75, 4718-4723. A PDMS material offers numerous attractive properties in microfluidic applications. Upon cross-linking, PDMS becomes an elastomeric material with a low Young's modulus, e.g., approximately 750 kPa. See Unger, M. A., et al., Science 2000, 288, 113-116. This property allows PDMS to conform to surfaces and to form reversible seals. Further, PDMS has a low surface energy, e.g., approximately 20 erg/cm2, which can facilitate its release from molds after patterning. See Scherer, A., et al., Science 2000, 290, 1536-1539; McDonald, J. C., et al., Acc. Chem. Res. 2002, 35, 491-499.
Another important feature of PDMS is its outstanding gas permeability. This property allows gas bubbles within the channels of a microfluidic device to permeate out of the device. This property also is useful in sustaining cells and microorganisms inside the features of the microfluidic device. The nontoxic nature of silicones, such as PDMS, also is beneficial in this respect and allows for opportunities in the realm of medical implants. McDonald, J. C., et al., Acc. Chem. Res. 2002, 35, 491-499.
Many current PDMS microfluidic devices are based on SYLGARD® 184 (Dow Corning, Midland, Mich., United States of America). SYLGARD® 184 is cured thermally through a platinum-catalyzed hydrosilation reaction. Complete curing of SYLGARD® 184 can take as long as five hours. The synthesis of a photocurable PDMS material, however, with mechanical properties similar to that of SYLGARD® 184 for use in soft lithography recently has been reported. See Choi, K. M., et al., J. Am. Chem. Soc. 2003, 125, 4060-4061.
Despite the aforementioned advantages, PDMS suffers from multiple drawbacks in microfluidic applications. First, PDMS swells in most organic solvents. Thus, PDMS-based microfluidic devices have a limited compatibility with various organic solvents. See Lee, J. N. et al., Anal. Chem. 2003, 75, 6544-6554. Among those organic solvents that swell PDMS are hexanes, ethyl ether, toluene, dichloromethane, acetone, and acetonitrile. See Lee, J. N., et al., Anal. Chem. 2003, 75, 6544-6554. The swelling of a PDMS microfluidic device by organic solvents can disrupt its micron-scale features, e.g., a channel or plurality of channels, and can restrict or completely shut off the flow of organic solvents through the channels. Thus, microfluidic applications with a PDMS-based device are limited to the use of fluids, such as water, that do not swell PDMS. As a result, those applications that require the use of organic solvents likely will need to use microfluidic systems fabricated from hard materials, such as glass and silicon. See Lee, J. N., et al., Anal. Chem. 2003, 75, 6544-6554. This approach, however, is limited by the disadvantages of fabricating microfluidic devices from hard materials.
Second, PDMS-based devices and materials are notorious for not being adequately inert to be used even in aqueous-based chemistries. For example, PDMS is susceptible to reaction with weak and strong acids and bases. PDMS-based devices also are notorious for containing extractables, such as extractable oligomers and cyclic siloxanes, especially after exposure to acids and bases. Because PDMS is easily swollen by organics, hydrophobic materials, even those hydrophobic materials that are slightly soluble in water, can partition during use into PDMS-based materials used to construct PDMS-based microfluidic devices.
Thus, an elastomeric material that exhibits the attractive mechanical properties of PDMS combined with a resistance to swelling in common organic solvents would extend the use of microfluidic devices to a variety of new chemical applications that are inaccessible by current PDMS-based devices. Accordingly, the approach demonstrated by the presently disclosed subject matter uses an elastomeric material, more particularly a functional perfluoropolyether (PFPE) material, which is resistant to swelling in common organic solvents to fabricate a microfluidic device.
Functional PFPE materials are liquids at room temperature, exhibit low surface energy, low modulus, high gas permeability, and low toxicity with the added feature of being extremely chemically resistant. See Scheirs, J., Modern Fluoropolymers; John Wiley & Sons, Ltd.: New York, 1997; pp 435-485. Further, PFPE materials exhibit hydrophobic and lyophobic properties. For this reason, PFPE materials are often used as lubricants on high-performance machinery operating in harsh conditions. The synthesis and solubility of PFPE materials in supercritical carbon dioxide has been reported. See Bunyard, W., et al., Macromolecules 1999, 32, 8224-8226. Beyond PFPEs, fluoroelastomers also can include fluoroolefin-based materials, including, but not limited to, copolymers of tetrafluoroethylene, hexafluoropropylene, vinylidene fluoride and alkyl vinyl ethers, often with additional cure site monomers added for crosslinking.
A PFPE microfluidic device has been previously reported by Rolland, J. et al. JACS 2004, 126, 2322-2323. The device was fabricated from a functionalized PFPE material (e.g., a PFPE dimethacrylate (MW=4,000 g/mol)) having a viscosity of the functionalized material of approximately 800 cSt. This material was end-functionalized with a free radically polymerizable methacrylate group and UV photocured free radically with a photoinitiator. In Rolland, J. et al., supra, multilayer PFPE devices were generated using a specific partial UV curing technique, however, the adhesion was weak and generally not strong enough for a wide range of microfluidic applications. Further, the adhesion technique described by Rolland, J. et al. did not provide for adhesion to other substrates such as glass.
The presently disclosed subject matter describes the use of fluoroelastomers, especially a functional perfluoropolyether as a material for fabricating a solvent-resistant micro- and nano-scale structures, such as a microfluidic device. The use of fluoroelastomers and functional perfluoropolyethers in particular as materials for fabricating a microfluidic device addresses the problems associated with swelling in organic solvents exhibited by microfluidic devices made from other polymeric materials, such as PDMS. Accordingly, PFPE-based microfluidic devices can be used in conjunction with chemical reactions that are not amenable to other polymeric microfluidic devices.
Further, adequate adhesion between the layers of a multilayer microfluidic device can impact performance in most if not all applications. For example, adhesion can impact performance in microfluidic devices, such as those described by Unger et al., Science, 288, 113-6 (2000), which contain multiple layers allowing for the formation of pneumatic valves. Thus, there is a need in the art for improved methods for adhering the layers of a microfluidic device together or to other surfaces.
Furthermore, many devices, such as surgical instruments, medical devices, prosthetic implants, contact lenses, and the like, are formed from polymeric materials. Polymeric materials commonly used in the medical device industry include, but are not limited to polyurethanes, polyolefins (e.g., polyethylene and polypropylene), poly(meth)acrylates, polyesters (e.g., polyethyleneterephthalate), polyamides, polyvinyl resins, silicone resins (e.g., silicone rubbers and polysiloxanes), polycarbonates, polyfluorocarbon resins, synthetic resins, polystyrene, various bioerodible materials, and the like. Although these and other materials commonly used as implant materials have proven to be useful there are many drawbacks with the materials. One drawback is that with any implant there is always the chance of bio-fouling on the surface of the implant. Bio-fouling can occur due to the tissue/implant interface gap and the surface characteristics of the implant material. Accordingly, a need exists for improving the polymeric materials and/or functionalizing the materials or the surface of the medical device materials to generate a better tissue/device interface and reduce bio-fouling.